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Research Labs: David D. Ho, M.D.
Basic and Clinical Development of Vaccines against HIV-1 Since 2001, my laboratory has focused on development of novel vaccines against HIV-1, both in the laboratory and in the clinic. Our first two candidate vaccines were ADAVX, a DNA-based multigenic clade C/B’ DNA-based vaccine, and ADMVA, a multigenic clade C/B’ vaccine utilizing the Modified Vaccinia Ankara virus. These vaccines have completed Phase I clinical testing and are moving towards larger trials in the People’s Republic of China. In 2006, we formed a consortium of scientists from ADARC (Drs. Yaoxing Huang, Moriya Tsuji), The Rockefeller University (Drs. Ralph Steinman, Jeffrey Ravetch, Michel Nussenzweig) and Mount Sinai School of Medicine (Drs. Peter Palese, Adolfo-Garcia-Sastre, and Thomas Moran) to develop novel vaccines with improved cellular and humoral immunogenicity by targeting dendritic cells. I serve as the PI for this Vaccine Discovery Center, funded by the Bill and Melinda Gates Foundation Collaboration for AIDS Vaccine Discovery. My laboratory focuses on multiple aspects of improving vaccine design and delivery. Through a combination of molecular epidemiology and analysis of serum from long term non-progressors, we are working to optimize envelope sequences to improve humoral immunogenicity and elicit neutralizing antibodies. In parallel, we are working to design and construct of viral-like particles (VLPs) targeted to dendritic cells by surface expression of CD40-L, and to create of novel viral vectors to evade pre-existing host immunity. We have a significant effort to enhancing the immunogenicity of DNA vaccines through delivery by in vivo electroporation (EP).With electroporation, standard intramuscular DNA injection is accompanied by application of a small, low voltage, localized electric field. This current provides a transient increase in membrane permeability to significantly enhance transfection efficiency of DNA plasmid into myocytes. The application of EP can enhance gene expression and immune responses following plasmid DNA vaccine delivery. We are currently conducting a Phase I clinical trial at the Rockefeller University to study the safety and immunogenicty of ADVAX when delivered by electroporation. China AIDS Initiative A Long and Winding Road Time Magazine, December 15, 2003
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